Tigecycline
Encyclopedia
Tigecycline (icon) is a glycylcycline
antibiotic
developed by Francis Tally and marketed by Wyeth
under the brand name Tygacil. It was given a U.S. Food and Drug Administration
(FDA) fast-track approval and was approved on June 17, 2005. It was developed in response to the growing prevalence of antibiotic resistance
in bacteria such as Staphylococcus aureus
and Acinetobacter baumannii
. The New Delhi metallo-β-Lactamase multidrug-resistant Enterobacteriaceae has also shown susceptibility to tigecycline.
of minocycline
. Tigecycline has a substitution at the D-9 position which is believed to confer broad spectrum activity.
by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of Aminoacyl-tRNA
into the A site of the ribosome during prokaryotic translation
.
and aztreonam
to treat complicated skin and skin structure infections (cSSSI), and to intravenous imipenem
and cilastatin to treat complicated intra-abdominal infections (cIAI). Tigecycline is active against many Gram-positive
bacteria, Gram-negative
bacteria and anaerobes – including activity against methicillin-resistant Staphylococcus aureus
(MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, and Neisseria gonorrhoeae (with MIC values reported at 2mcg/mL) and multi-drug resistant strains of Acinetobacter baumannii
. It has no activity against Pseudomonas
spp. or Proteus
spp. The drug is licenced for the treatment of skin and soft tissue infections as well as intra-abdominal infections.
s to the tetracyclines. The most common side effects of tigecycline are diarrhea, nausea and vomiting. Nausea and vomiting is mild or moderate and usually occurs during the first two days of therapy. Other side effects include pain at the injection site, swelling and irritation; increased or decreased heart rate and infections. Also avoid use in children and pregnancy, due to its effects on teeth and bone. As with other antibiotics, overgrowth of organisms that are not susceptible to tigecycline can occur.
Tigecycline showed an increased mortality in patients treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia, but also in patients with complicated skin and skin structure infections, complicated intra-abdominal infections and diabetic foot infection.
Glycylcycline
Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
developed by Francis Tally and marketed by Wyeth
Wyeth
Wyeth, formerly one of the companies owned by American Home Products Corporation , was a pharmaceutical company. The company was based in Madison, New Jersey, USA...
under the brand name Tygacil. It was given a U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) fast-track approval and was approved on June 17, 2005. It was developed in response to the growing prevalence of antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
in bacteria such as Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
and Acinetobacter baumannii
Acinetobacter baumannii
Acinetobacter baumannii is a species of pathogenic bacteria, referred to as an aerobic gram-negative bacterium, that is resistant to most antibiotics. As a result of its resistance to drug treatment, some estimates state the disease is killing tens of thousands of U.S...
. The New Delhi metallo-β-Lactamase multidrug-resistant Enterobacteriaceae has also shown susceptibility to tigecycline.
Structure
This antibiotic is the first clinically-available drug in a new class of antibiotics called the glycylcyclines. It is structurally similar to the tetracyclines in that it contains a central four-ring carbocyclic skeleton and is actually a derivativeDerivative
In calculus, a branch of mathematics, the derivative is a measure of how a function changes as its input changes. Loosely speaking, a derivative can be thought of as how much one quantity is changing in response to changes in some other quantity; for example, the derivative of the position of a...
of minocycline
Minocycline
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...
. Tigecycline has a substitution at the D-9 position which is believed to confer broad spectrum activity.
Mechanism of action
Tigecycline is bacteriostatic and is a protein synthesis inhibitorProtein synthesis inhibitor
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins....
by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of Aminoacyl-tRNA
Aminoacyl-tRNA
Aminoacyl-tRNA is tRNA to which its cognated amino acid is adhered. Its role is to deliver the amino acid to the ribosome where it will be incorporated into the polypeptide chain that is being produced...
into the A site of the ribosome during prokaryotic translation
Prokaryotic translation
Prokaryotic translation is the process by which messenger RNA is translated into proteins in prokaryotes.-Initiation:Initiation of translation in prokaryotes involves the assembly of the components of the translation system which are: the two ribosomal subunits , the mRNA to be translated, the...
.
Indications
Tigecycline is given intravenously and has activity against a variety of gram-positive and gram-negative bacterial pathogens, many of which are resistant to existing antibiotics. Tigecycline successfully completed phase III trials in which it was at least equal to intravenous vancomycinVancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
and aztreonam
Aztreonam
Aztreonam is a synthetic monocyclic beta-lactam antibiotic , with the nucleus based on a simpler monobactam isolated from Chromobacterium violaceum. It was approved by the U.S. Food and Drug Administration in 1986...
to treat complicated skin and skin structure infections (cSSSI), and to intravenous imipenem
Imipenem
Imipenem is an intravenous β-lactam antibiotic developed in 1980. It has an extremely broad spectrum of activity.Imipenem belongs to the subgroup of carbapenems. It is derived from a compound called thienamycin, which is produced by the bacterium Streptomyces cattleya...
and cilastatin to treat complicated intra-abdominal infections (cIAI). Tigecycline is active against many Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria, Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria and anaerobes – including activity against methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, and Neisseria gonorrhoeae (with MIC values reported at 2mcg/mL) and multi-drug resistant strains of Acinetobacter baumannii
Acinetobacter baumannii
Acinetobacter baumannii is a species of pathogenic bacteria, referred to as an aerobic gram-negative bacterium, that is resistant to most antibiotics. As a result of its resistance to drug treatment, some estimates state the disease is killing tens of thousands of U.S...
. It has no activity against Pseudomonas
Pseudomonas
Pseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
spp. or Proteus
Proteus (bacterium)
Proteus is a genus of Gram-negative Proteobacteria.-Clinical significance:Three species—P. vulgaris, P. mirabilis, and P. penneri—are opportunistic human pathogens. Proteus includes pathogens responsible for many human urinary tract infections. P. mirabilis causes wound and urinary...
spp. The drug is licenced for the treatment of skin and soft tissue infections as well as intra-abdominal infections.
Dosing
Tigecycline is given by slow intravenous infusion (30 to 60 minutes). A single dose of 100 mg is given first, followed by 50 mg every twelve hours after that. Patients with impaired liver function need to be given a lower dose. No adjustment is needed for patients with impaired kidney function. It is not licensed for use in children. There is no oral form available.Side effects
Tigecycline has similar side effectAdverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s to the tetracyclines. The most common side effects of tigecycline are diarrhea, nausea and vomiting. Nausea and vomiting is mild or moderate and usually occurs during the first two days of therapy. Other side effects include pain at the injection site, swelling and irritation; increased or decreased heart rate and infections. Also avoid use in children and pregnancy, due to its effects on teeth and bone. As with other antibiotics, overgrowth of organisms that are not susceptible to tigecycline can occur.
Tigecycline showed an increased mortality in patients treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia, but also in patients with complicated skin and skin structure infections, complicated intra-abdominal infections and diabetic foot infection.